The long-range objectives of this researcher are to understand the biochemical processes of neuronal and behavioral plasticity. The explicit strategy assumes that the understanding of such phenomena will emerge from an understanding of plastic events at the synapse. This proposal presents an approach to investigate presynaptic mechanisms of plasticity in brain. The research will attempt to establish an in vitro model for investigating synaptic plasticity in brain. Endogenous dopamine release from striatal synaptosomes will be investigated. Using a previously established biochemical technique for studying stimulus-secretion coupling processes from isolated nerve-ending particles, an attempt will be made to elucidate the mechanisms for stimulation-dependent depression of calcium-dependent, endogenous dopamine release.